1. Field of the Invention
The present invention provides comprehensive compositions for treating The problems associated with hair graying and balding via the incorporation of: (i) Cell growth factor of HSCF to induce the migration of melanocyte stem cells and keratinocyte stem cells and then to increase the growth of melanocytes and keratinocytes in hair follicles, (ii) a formula of amino acids and vitamins to provide the nutritional factors for hair growth and pigmentation, and (iii) minoxidil to enhance the function of HSCF on hair re-growth. The compositions comprising at least one of (i), (ii) or (iii) are administered on skin and/or scalp through the liposome in the follicular delivery systems, including penetration enhancers and suitable carrier bases. The composition packaged in liposome in the follicular delivery systems of this invention has been proven to reach the dermis from the skin surface within 15-30 min. The essential function of the liposome is to maintain the activity of the growth factor of HSCF for at least one to three years.
2. Description of the Prior Art
Dual therapies of hair graying and balding in topical delivery systems have never been claimed in the market. When a graying hair derives in large part from a mixture of pigmented and white hair, it can clearly be noted that individual hair follicles indeed exhibit pigment dilution or true graying. This dilution could be due to a reduction in tyrosinase activity of hair bulbar melanocytes, sub-optimal melanocyte-cortical keratinocyte interaction, or defective migration of melanocytes from a reservoir in the upper outer root sheath to the pigment-permitting microenvironment close to dermal papilla of the hair bulb(12). Some studies have reported that stem cell factor (SCF) has the functions to proliferate and migrate to the melanoblasts and keratinoblasts restored in the upper outer root sheath, called hair bulge(1, 2). These melanoblasts and keratinoblasts, called melanocyte and keratinocyte stem cells, respectively, in hair bulge, could proliferate and migrate to dermal papilla in hair bulb and then differentiate to become melanocytes and keratinocytes(12, 13, 14). Hair pigmentation is mostly produced by melanin accumulation, which is secreted from melanocytes(12, 16). And hair shaft is mostly produced by keratin accumulation, which is secreted from keratinocytes. This growth factor of SCF has been proven to stimulate stem cells in hair bulge(3, 6, 9). However, mice with homozygous SCF gene mutation (SL−/SL−) show the symptoms of white hair, infertility, and anemia(1, 5). It suggests the importance of SCF in hair pigmentation(7, 13), but effects on hair growth are limited because the mutated mice still have hair. In addition, many growth factors and signals through different pathways control the hair growth. Especially, insulin-like growth factor-I (IGF-I) has been reported to induce growth of hair in many papers(4, 15). Based on our previous data, the same results have also been obtained. Although the amino acid sequence and protein structure of recombinant human SCF has been clearly studied(17) and also been applied as a patent (U.S. Patent Publication No.: 20050080250, application Ser. No. 10/620,642, filed: Jul. 16, 2003. Methods of stimulating growth of stromal cells in a human.), SCF and other ingredients are incorporated to claim the dual therapies for hair aging in our experimental data.
The combination of the two growth factors, SCF and IGF-I, has been studied to have the more advanced functions on the hair follicles in our study, because it significantly stimulates the hair growth and melanin synthesis at the same time. We gave the definition of the two growth factors of SCF and IGF-I as HSCF (hair stem cell factor), meaning either the combination, named HSCF-I, or the recombinant protein, named HSCF-II. The recombinant protein of HSCF-II is first established by our group, which is produced by a cloning vector inserted with a combination of human SCF and IGF-I sequence together. The medium containing HSCF results in a higher increase of shaft length of mouse hair follicles cultured in vitro, when compared with SCF or IGF-I alone. After the above compositions are administered along with a hair follicular delivery vehicle and/or device on the skin of mice, longer hair length and darker pigmentation of hair shaft are obtained.
Minoxidil, being a potassium channel opener, has been proven to induce human hair growth from many papers and is popular in the market to treat patients with androgenic alopecia. But the effects of minoxidil on treating hair balding are still limited(10). The functions of minoxidil could reduce continuous hair loss, but couldn't increase hair amount and density or recover the pigment of graying hair. We tried to amplify the function of minoxidil by adding the above compositions, because it has been proven by the inventors of this invention that HSCF could stimulate the stem cells in hair bulge to migrate into hair bulb, and then differentiate to melanocyte and keratinocyte to regenerate a newly pigmented hair in a hair follicle.
The results showed that compositions of (i) HSCF, (ii) a formula of some amino acids and vitamins, and (iii) minoxidil could achieve the best efficiency on hair growth and melanin synthesis. It also has been proven to treat the graying and balding problems by the in vitro culture of hair follicle organ and also by the in vivo animal models of graying and balding mice. The invention could be further applied to treat the hair aging of human beings.